TOXICITY OF CARBON NANOTUBES - Carbon Nanotubes: From Bench Chemistry to Promising Biomedical Applications - page 232

Lam et al. 45 and Warheit et al. 46 were among the irst to investigate the
pulmonary toxicity of CNTs (speciically SWCNTs) in rodents. In particular,
Lam et al. evaluated histopathological alterations in mice at 7 and 90 days
after exposure to three differently manufactured SWCNTs that contained
varying amounts of residual catalytic metals: (i) raw nanotubes (RNTs) and
(ii) puriied nanotubes (PNTs), both iron-containing HiPCO products from
Rice University, and (iii) CarboLex's nickel-containing electric-arc nanotubes
(CNTs). Carbon black and quartz were employed as low and high pulmonary
toxicity controls, respectively. The experiments indicated that the three types
of tubes induced dose-dependent lung lesions, consisting on interstitial
granulomas, regardless of the amount of metal impurities inside the samples. 45
Even in case of low quantities of iron (2% by weight) granulomas were formed,
suggesting that CNTs themselves are toxic. However, the methods employed
for this study were somehow unclear, since the suspension was obtained by
briely shearing and short sonication to avoid any alteration of the nature of
SWCNTs, but the instillation was performed through a plastic catheter placed
in the trachea. So further studies would be needed to elucidate the cause
of death. However, it was clear that mice treated with 0.5 mg of nanotubes
showed the formation of granulomas, containing macrophages laden with
black particles, a few lymphocytes, neutrophils, eosinophils and other
inlammatory cells. Interestingly, the lowest dose (0.1 mg/30 kg) determined
no evident clinical signs. The same (5 mg/kg), or even a lower (1 mg/kg),
amount of SWCNTs was employed in the study by Warheit et al. in which
histopathological evaluation of lung tissue was conducted after 24 hours, 1
week and 3 months post-instillation in rats. 46 In these experiments, SWCNTs
and graphite particles, together with the corresponding controls (carbonyl
iron and quartz particles), were intratracheally instilled in the animals. In
the case of carbonyl iron or graphite, no adverse effects were observed, while
non-dose-dependent multifocal granulomas were visible after exposure to
SWCNTs, even if they did not progress beyond 1 month. In 15% of the rats, the
highest dose induced mortality, but the main reason of that was imputable to
the mechanical blockage of the upper airways, and not to the inner toxicity
of SWCNT particulate. The death index was somehow incorrect, because the
nanotubes tended to form nanoropes instead of being individually dispersed.
A proof was the observation that the survived animals appeared normal
through the whole 3 months. In addition, studies on chemotaxis concerning
quartz treatment showed a reduced motility as a consequence of a deiciency
in macrophages after 1 week. This phenomenon was not observed in the case
of SWCNTs, which differed from quartz also in the formation of granulomas
in a non-dose-dependent manner.